Classical schemes of the adult Schistosoma mansoni reproductive system have been described. In our study, whole adult worms derived from unisexual or mixed infections and stained with carmine chlorine were virtually and tomographically analyzed under confocal laser scanning microscopy. We found that: (1) there were morphological differences in the ovary, vitteline glands and testicular lobes between specimens derived from unisexual or mixed infections; (2) there was always a single lobed ovary (three or four lobes), presenting differentiation from the anterior to the posterior lobes, where the most mature oocytes were located; (3) the proximal segment of oviduct was connected to an ampullary dilatation, full of tailed spermatozoa, characterizing a seminal receptacle; (4) there was no long vitelline duct, but a short one that begins at the end of the proximal region of the vitelline gland; (5) long cells of Mehlis' gland placed radially around the ootype were not observed. Otherwise, the ootype was only lined by thick cuboidal epithelial cells with plaited bases and nuclei with flabby chromatin, making a clear distinction from the uterine epithelium. This morphological feature suggests that each cell represents a gland. (6) In coupled males, the specimens located inside the gynaecophoric canal had smaller testicular lobes, suckers, and body length and width when compared to their partners. Our results show that the reproductive system does not follow a unique pattern within flatworms. Due to its better resolution, confocal laser scanning microscopy, using a reflected mode with tomographic sections, allows new interpretations, modifying the adopted and current descriptions of the internal morphological structures of S. mansoni adult worms.

BackgroundProtein kinases are proven targets for drug development with an increasing number of eukaryotic Protein Kinase (ePK) inhibitors now approved as drugs. Mitogen-activated protein kinase (MAPK) family members connect cell-surface receptors to regulatory targets within cells and influence a number of tissue-specific biological activities such as cell proliferation, differentiation and survival. However, the contributions of members of the MAPK pathway to schistosome development and survival are unclear.Methodology/Principal FindingsWe employed RNA interference (RNAi) to elucidate the functional roles of five S. mansoni genes (SmCaMK2, SmJNK, SmERK1, SmERK2 and SmRas) involved in MAPK signaling pathway. Mice were injected with post-infective larvae (schistosomula) subsequent to RNAi and the development of adult worms observed. The data demonstrate that SmJNK participates in parasite maturation and survival of the parasites, whereas SmERK are involved in egg production as infected mice had significantly lower egg burdens with female worms presenting underdeveloped ovaries. Furthermore, it was shown that the c-fos transcription factor was overexpressed in parasites submitted to RNAi of SmERK1, SmJNK and SmCaMK2 indicating its putative involvement in gene regulation in this parasite's MAPK signaling cascade.ConclusionsWe conclude that MAPKs proteins play important roles in the parasite in vivo survival, being essential for normal development and successful survival and reproduction of the schistosome parasite. Moreover SmERK and SmJNK are potential targets for drug development.

Malnutrition hampers the course of schistosomiasis mansoni infection just as normal growth of adultKey words: Schistosoma mansoni -undernutrition -confocal scanning laser microscopy Schistosomiasis is a very widespread disease in the developing world and is one of the most important helminth infections. Malnutrition and schistosomiasis mansoni are both serious publichealth problems in Northeast Brazil and often overlap in the same geographical area (Coutinho et al. 1997a). Meanwhile, the role played by the nutritional status of the host on the development of schistosomiasis and vice versa is not clearly understood (Ferreira & Coutinho 1999

A computer software for image analysis (IMAGE PRO PLUS, MEDIA CYBERNETICS)

A comparative morphometric study was performed to identify host-induced morphological alterations in

Eukaryotic protein kinases (ePKs) are good medical targets for drug development in different biological systems. ePKs participate in many cellular processes, including the p38 MAPK regulation of homeostasis upon oxidative stress. We propose to assess the role of Smp38 MAPK signaling pathway in Schistosoma mansoni development and protection against oxidative stress, parasite survival, and also to elucidate which target genes have their expression regulated by Smp38 MAPK. After a significant reduction of up to 84% in the transcription level by Smp38 MAPK gene knockdown, no visible phenotypic changes were reported in schistosomula in culture. The development of adult worms was tested in vivo in mice infected with the Smp38 knocked-down schistosomula. It was observed that Smp38 MAPK has an essential role in the transformation and survival of the parasites as a low number of adult worms was recovered. Smp38 knockdown also resulted in decreased egg production, damaged adult worm tegument, and underdeveloped ovaries in females. Furthermore, only ~13% of the eggs produced developed into mature eggs. Our results suggest that inhibition of the Smp38 MAPK activity interfere in parasites protection against reactive oxygen species. Smp38 knockdown in adult worms resulted in 80% reduction in transcription levels on the 10th day, with consequent reduction of 94.4% in oviposition in vitro. In order to search for Smp38 MAPK pathway regulated genes, we used an RNASeq approach and identified 1,154 DEGs in Smp38 knockdown schistosomula. A substantial proportion of DEGs encode proteins with unknown function. The results indicate that Smp38 regulates essential signaling pathways for the establishment of parasite homeostasis, including genes related to antioxidant defense, structural composition of ribosomes, spliceosomes, cytoskeleton, as well as, purine and pyrimidine metabolism pathways. Our data show that the Smp38 MAPK signaling pathway is a critical route for parasite development and may present attractive therapeutic targets for the treatment and control of schistosomiasis.

High-fat diets induce weight gain and fatty liver in wild-type mice. Schistosomiasis mansoni infection also promotes hepatic injury. This study was designed to quantify hepatic alterations in schistosomiasis mansoni infected mice fed a high-fat diet (IHFC) or standard chow (ISC), uninfected mice fed a high-fat diet (HFC) or standard chow (SC). Mice were sacrificed during early infection (9 weeks from exposure). The following hepatic biometry and the stereology parameters were determined: volume density (hepatocytes [h], sinusoids [s], steatosis [st] and hepatic fibrosis [hf]); numerical density (hepatocyte nuclei -Nv[h]); absolute number of total hepatocyte N[h], normal hepatocyte N[nh], and binucleated hepatocyte N[bh], percentage of normal hepatocyte P[nh] and binucleated hepatocyte P[bh]. IHFC and HFC groups exhibited TC, HDL-C, LDL-C, and body mass significantly greater (p < 0.05) than control group. No significant differences were found regards liver volume (p = 0.07). Significant differences were observed regards P[nh] (p = 0.0045), P[bh] (p = 0.0045), Nv[h] (p = 0.0006), N[h] (p = 0.0125), N[bh] (p = 0.0164) and N[nh] (p = 0.0078). IHFC mice group presented 29% of binucleated hepatocytes compared to HFC group (19%), ISC group (17%) and SC (6%

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